1. Field of the Invention
The invention relates to methods for the treatment of dermatological conditions in humans and animal via the controlled application of heat. In certain embodiments, the invention relates to methods of treating dermatological conditions caused or exacerbated by bacterial infection, and in particular, methods for the treatment of acne. The invention also relates to devices for the controlled application of heat for use in methods for treating dermatological conditions.
2. Description of Related Art
Skin infections and irritations pose significant health and cosmetic problems. Bacterial and fungal skin infections lead to common lesions such as acne, pimples and under-nail fungal infections. Other lesions are caused by irritants, which may be introduced as a result of bug bites or by exposure to other natural or man-made skin irritants. Still other skin lesions are caused by viral infection, a common example being the lesions known as “cold sores” or “fever blisters”. These skin lesions are often unsightly and painful, and current methods of treatment are often inadequate.
Pustular eruptions, localized abscessed formation and local inflammatory conditions of the dermis and epidermis represent a particularly significant cosmetic and health problem. One of the most common afflictions of this type are lesion caused by the condition known as acne vulgaris. Acne vulgaris is associated with the Gram-positive anaerobic bacterium, Propionibacterium acnes. Acne afflicts 90% of all teenagers, and often continues to afflict men and women in the second, third and forth decade of life, sometimes persisting throughout adulthood. (Yonkosky, D. M. and P. E. Pochi, Acne vulgaris in childhood. Pathogenesis and management. Dermatol Clin, 1986. 4(1): p. 127–36.) Abscess formation from a number of primarily bacterial species (commonly Staphylococcus and Streptococcus) as well as fungal species, such as dermatophytes, are a less frequent medical and cosmetic problem but share similar challenges regarding effective treatment.
Setting the scene of acne and other skin infections, endogenous hormones (mainly androgens), which are present in unusually high concentrations in the blood during adolescence and puberty, give rise to an excessive production of sebum. This condition may worsen by a simultaneous increase in the rate of keratinization of the skin's horny layer (the stratum corneum). As the horny cells proliferate, they can form an occlusive plug or comedone which, coupled with the increased production of the sebum, represents an ideal medium for the proliferation of bacterial strains frequently resident on skin, such as P. acnes. 
In acne vulgaris, plugged follicles eventually rupture, allowing discharge of their contents and causing local swelling and inflammation. The exposed follicles may darken from the deposition of pigment from damaged cells in the deeper layer of skin.
Acne vulgaris is therefore a chronic disorder of the pilosebaceous follicles characterized by comedones (blackheads), papules, pustules, cysts, nodules, and often results in the formation of permanent scars (Cunliffe, W. J., et al., Comedogenesis: some aetiological, clinical and therapeutic strategies. Dermatology, 2003. 206(1):11–6) that appear on the most visible areas of the skin particularly on the face, chest, back and occasionally neck, and upper arms. It is known that P. acnes also produces low-molecular-weight chemotactic factors which attract leukocytes, thereby causing or enhancing inflammation (Scholdgen, W., Hautarzt, 1965. 16(11):518–20; Lever, L. and R. Marks, Drugs, 1990. 39(5):681≠92). This increased inflammatory process, if left untreated, can produce significant immediate and long-term cosmetic problems including permanent scar formation.
Acne is a multistage condition. In its most severe form it leads to hospitalization of the patient, extensive discomfort and long term scarring of the skin.
Multiple treatment options have been available for acne and localized abscess formations (Scholdgen, W., Hautarzt, 1965. 16(11):518–20; Lever, L. and R. Marks, Drugs, 1990. 39(5):681–92) since the early 1960's, however no one drug appears effective against all distinctive types of acne or abscess formation and most preparations have significant side effects. (Russell, J. J., Am Fam Physician, 2000. 61(2):357–66.) Comedolytic agents, for example, promote comedonal drainage but also cause significant skin irritation. Topical antibiotics decrease the number of mild to moderate inflammatory lesions by inhibiting the growth of P. acnes and are also associated with skin irritation, dryness, and potential antibiotic resistance as well as potential overgrowth of fungal or yeast infections. (Gollnick, H. P. and A. Krautheim, Dermatology, 2003. 206(1):29–36.) Oral antibiotics are the standard for treating moderate to severe acne lesions, however, superinfection may occur with long-term exposure and may require routine laboratory monitoring. Antibiotic treatment against P. acnes has been the mainstay of treatment for more than 40 years. (Loveckova, Y. and I. Havlikova, Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2002. 146(2):29–32.) Despite the widespread use of systemic antibiotics such as tetracyclines, erythromycins (Vermeulen, B., J. P. Remon, and H. Nelis, Int J Pharm, 1999. 178(1):137–41) and clindamycins (Rizer, R. L., et al., Clindamycin phosphate 1% gel in acne vulgaris. Adv Ther, 2001. 18(6):244–52) as the most common, changes in the sensitivity of P. acnes to antibiotics has been seen for the last two decades. A number of mutations have been characterized which lead to increased resistance of P. acnes to both systemic and topical antibiotic treatments.
Another widespread treatment option for P. acnes has been the use of oral Vitamin A acid derivatives such as cis-Retinioc Acid (Accutane). However, the use of cis-Retinoic Acid has been reserved for severe cases of acne vulgaris since significant side effects can be seen with the use of cis-Retinioc acid. (Thorne, E. G., Br J Dermatol, 1992. 127 Suppl 41:31–6.) Some of these side effects include liver toxicity, severe skin drying, increase sensitivity to UV radiation, elevations in triglicyride and cholesterol levels, as well as mood changes including severe depression. Again, cis-Retinoic Acid has been reserved for severe or refractory cases of acne vulgaris.
In addition to prescription medications for the treatment of acne vulgaris, a number of over the counter topical preparations are widely used as well. (Scholdgen, W., Z Allgemeinmed, 1972. 48(17):833–5; Melski, J. W. and K. A. Arndt, Current concepts: topical therapy for acne. N Engl J Med, 1980. 302(9):503–6; Lester, R. S., Topical formulary for the pediatrician. Pediatr Clin North Am, 1983. 30(4):749–65; Broniarczyk-Dyla, G. and C. Arkuszewska, Dermatol Monatsschr, 1989. 175(1):40–3; Zander, E. and S. Weisman, Treatment of acne vulgaris with salicylic acid pads. Clin Ther, 1992. 14(2):247–53; Kaye, E. T. and K. M. Kaye, Topical antibacterial agents. Infect Dis Clin North Am, 1995. 9(3):547–59.)
These include, broadly, drying agents, oxidizing agents and astringents, also a wide variety of skin detergents and cleansers, as well as preparations, which attempt to form oxidizing agents which are reportedly toxic to P. acnes. 
Other treatment methods that have been suggested include the methods disclosed in U.S. Pat. No. 6,183,500 involving the use of phototherapy in the treatment of acne vulgaris, whereby a concentrated light source is used as a treatment. Additionally, ultrasound devices to deliver energy in a localized fashion have also been decribed. (Ruiz-Esparza, J. and J. B. Gomez, Dermatol Surg, 2003. 29(4):333–9; discussion 339.) Even attempt of using cautery with local anesthesia has been described. (Pepall, L. M., M. P. Cosgrove, and W. J. Cunliffe, Br J Dermatol, 1991. 125(3):256–9.) Many of these devices require expensive and unwieldy equipment, and treatment by a physician.
Other types of bacterial skin lesions include bacterial folliculitis, (a localized infection of hair follicles) dermatitis, cellulitis, impetigo, ecthyma, furuncles and the like.
It has long been known that the application of heat to both pustular eruptions as well as localized abscesses can be an effective way to treat these conditions. The most common method employed uses hot compresses, which generally must be applied multiple times throughout the day to be even marginally effective. Often the use of hot compresses is recommended to alleviate discomfort by “popping” pimples and other pustular eruptions and allowing them to drain. Although it is well-known that the application of heat is toxic to multiple forms of bacteria, including P. acnes and Staphylococcus species, the use of hot compresses has shown limited utility in the treatment of skin lesions such as acne. In fact, many clinicians disfavor hot compresses because they are believed to aggravate acne. Furthermore, hot compresses are generally non-uniform in the amount of heat delivered. Over-heating of the compresses by the user may easily result in burns. Other disadvantages include the fact that hot compresses generally only maintain heat for a very limited period of time, and when moved about or reused may result in spread of infectious agents to healthy tissue.
A further type of skin lesion that has proved difficult to treat are viral skin lesions such as cold sores, also known as fever blisters. Cold sores are usually caused by strains of the Herpes Simplex virus and commonly result in lesions on and near the lips and inside the mouth of an infected individual. The sores are painful and unsightly, and like other facial lesions, frequently result in psychological stresses for the patients suffering from the condition. The eruption of the sores is often, but not always, preceded by a painful sensation that warns of an impending lesion.
Various ointments and skin treatments exist that may be used to reduce the painful symptoms of the sores and to decrease the time for the sores to heal. Certain anti-viral medications, such as Acyclovir and Famvir, may also be used to prevent outbreaks and reduce healing time. However these medications are generally expensive and only available with a prescription. Furthermore, they may result in adverse side effects such as renal toxicity and therefore physicians are sometimes reluctant to prescribe these medications for simple outbreak cases. Also, to effectively prevent a cold sore outbreak, the medications usually must be taken prophylactically or upon the first sign of an outbreak. Once the sore has erupted, the lesions generate infectious particles which may in turn infect other individuals. Alkali inhibition is commonly used for laboratory inhibition of Herpes viruses, but application of alkali is impractical in a clinical setting due to the harshness of the treatment to normal skin.
A further type of skin lesion are fungal infections, also known as fungal dermatitis, including conditions known medically as Tinea corporis, Tinea pedis, Tinea unguium, Tinea capitis, Tinea cruris, and Tinea barbae. Particularly troublesome is the condition known as Tinea unguium which is a fungal infection occuring under toenails or fingernails, a condition also referred to medically as onychomycosis or ringworm of the nails. Onychomycosis may be caused by several types of fungi, including Trichophyton mentagrophytes, Candida albicans or Trichophyton rubrum. Such infections are extremely difficult to treat effectively due to the difficulty in delivering effective amounts of antifungal medications to the area beneath the nail.
Onychomycosis can cause the nail to appear thickened and lusterless, and often causes nail discomfort. Also, the infected nail harbors a reservoir of pathogenic organisms which can spread to and re-infect other parts of the body, causing chronic diseases such as onychomycosis in other nails, athletes foot, foot dry skin and the like. Onychomycosis is prevalent throughout a large proportion of the population, with most of those afflicted from the ages of 40 years and older.
A human's nail has a nail plate, which is a hard outer surface of dead cells, and a nail bed below the nail plate. The nail plate is non-porous, whereas the nail bed is porous. There is soft flesh beneath the nail bed. The nail plate and the nail bed are relatively insensitive to pain. The underlying flesh is sensitive to pain. In onychomycosis, the nail plate, nail bed, and, in severe cases, the flesh below the nail bed can be infected.
Methods of treating onychomycosis include various methods of delivering medication to the nail bed, including various methods of introducing medication under or through the nail plate or of removing the nail plate partially or entirely to access the infected tissue. Other treatments include systemic anti-fungal medications. The difficulty with systemic medications is that they are not localized to the nail area and therefore it is difficult to achieve an effective dose without producing undesirable side effects in other parts of the body.
Tinea corporis, also known as tinea circinata or tinea glabrosa and referred to generally as ringworm of the body, is a fungal infection or dermatophytosis of the glabrous skin, i.e., areas of skin other than bearded area, scalp, groin, hands and feet, generally caused by fungal species such as those of Microsporum such as Microsporum canis, Trichophyton such as Trichophyton rubrum, T. Mentagrophytes, and Epidermophyton, particularly by the fungal species of Trichophyton and Epidermophyton. The condition generally includes the presence of one or more well-demarcated erythematous, scaly mascules with slightly raised borders and central healing, producing annular outlines. Various other types of lesions may also occur, such as those that are vesicular, eczematous, psoriasiform, verrucous, plaque-like, or deep.
Tinea cruris, also referred to generally as “jock itch” or ringworm of the groin, is a fungal infection or dermatophytosis of the groin, perineum and perineal regions, generally seen in males, and sometimes spreading to contiguous areas, generally caused by fungal species such as those of Microsporum, Trichophyton, and Epidermophyton, particularly by the fungal species of Trichophyton and Epidermophyton. The condition generally includes severely pruritic, sharply demarcated lesions with a raised erythematous margin and thin, dry scaling. Tinea cruris often accompanies tinea pedis (also known as “athlete's foot”).
Tinea pedis results in interdigital lesions. Athlete's foot is an itching, malodorous, uncomfortable disorder resulting from large numbers of ordinary, nonvirulent bacteria proliferating in the fungus infected interspace.
Certain insect bites and contact with certain plants can expose skin to irritants that result in an itchy or painful immune response. The symptoms generally manifest soon after the introduction of the irritant, but can persist or sporadically reoccur for extended periods of time when the irritant is not effectively removed or inactivated by the immune response. Various treatments have been proposed for the treatment of the symptoms caused by these irritants. Typically the treatment involves that application of compounds that inhibit the immune response that generates the itching and inflammation usually associated with these conditions. These compounds tend to mask the symptoms of the insect bite without addressing the root cause of the irritation. They also tend to require repeated applications in order to obtain continuous symptom relief and frequently do not speed healing time in any appreciable manner.
For insect bites, a device has recently been marketed that is known as an “ItchZapper™”. This device allegedly treats insect bites by applying one or more bursts of heat to the area of the bite thereby breaking down the irritants introduced by the insect bite and stopping the release of histamine. The device represented as heating to a temperature of 122° F., and insect proteins are said to break down at 118° F. The present inventors have tested this device and found it to be deficient for the treatment of insect bites in several respects. The ItchZapper™ device examined by the inventors rapidly heated to a peak temperature over a period of 2 to 4 seconds. The device cooled as residual heat bled off the device for a few seconds after the heating cycle was completed. The upward and downward ramping of the temperature was pronounced and the device was not capable of holding a sustained temperature for any appreciable period of time. The device never ramped to the same temperature twice, and when tested multiple times over relatively short period of time, the temperature often ramped beyond thermic damage for human skin (i.e. the device was capable of burning a subject). The total heating period for the device is well under 10 seconds. The extremely brief treatment period is unlikely to have any appreciable effect on insect bite symptoms without repeated treatments.
There is therefore a need for improved treatments for skin lesions caused by bacterial, viral and fungal infections and by exposure to irritants such as those introduced by insect bites and poisonous plants, particularly treatments that will effectively ameliorate the symptoms of the lesions and promote healing without causing adverse effects in the majority of patients.